December 20th, 2021

1) It appears that omicron is everywhere in the US now, as expected.
2) Hospitalizations and deaths remain decoupled from cases meaning that we are on our way to mild COVID endemicity.
3) Your risk of death if you have had covid naturally or been vaccinated appears now to be very very very low with Omicron or Delta.
4) The caveat to number three is that if you are older with co-morbid disease in a significant stage, your risk of death is much higher. But, this is true for influenza and other severe viral illnesses as well at this point because of the inflammation that pervades the body from these diseases over time.

5) There are two new antivirals that may reduce the risk of four.
6) Lifestyle alterations now will definitely reduce your all cause mortality risk including covid.
7) Boosting is a serious question mark at this time. We need more data on how pathologic the breakthrough infections are with regards to disease morbidity not just spread. I.e. we need hospital data based on age and disease risk. A positive test with mild symptoms may be just that. We have no a priori knowledge of the long term risks of three mRNA vaccines in a calendar year. As always, to boost is a personal choice based on the science, age and risk. Getting vaccinated if not already vaccinated makes incredible sense at this point.
8) The rest of the world needs vaccine now to slow the mutability of the virus in general.
9) Please keep all schools open regardless of spread unless we see an increase in hospitalizations and deaths.
10) MOST IMPORTANT - Every decision from here on out has to have the mental health of humans as part of the calculus. Fear of COVID is not a good decision making guidance tool now and likely never was. Risk calculation and personal health is important. I was speaking to some medical students this am about their personal fear of COVID. They should have none. They are young, healthy and vaccinated. Risk is less than almost anything else that we do on a daily basis including log fold less than driving a car. Keep everything in context now.


Here are some quality words from Dr. Monika Ghandhi

"Dear Readers,

The last few weeks since Thanksgiving have been a roller coaster with a lot of panicked reporting about Omicron that seems to be settling – Omicron more transmissible, most likely, but all evidence points out to more mild infection (presumably due to more immunity although cannot rule out less virulent) and all reports very different than Delta emergence. Holidays can be spent together with this news & important to have nuanced, harm reduction approach starting in 2022 to COVID-19.

Thanks, Monica "

I could not agree more. Spend a loving and social holiday season with your loved ones. Really give thanks for survival and the beauty of this country. Hug your kids often even when they are imperfect and/or frankly pains. Hugs and love will cure almost all ills including teenager brain! I have decided that I can do much more with hugs and love than I can with directives and pressure in this age group.


Marty Makary MD, MPH states: "The immediate reflex to give young healthy people a 3rd vaccine dose to protect against Omicron is not supported by data, nor is it necessary for anyone who has natural immunity based on the studies we have to date".


Quick Hits - Data on Omicron is coming in!

1) Omicron is vastly more infectious than Alpha and Delta. Unite Kingdom officials have pegged the in home spread rate of Omicron to be 3X that of Delta which is impressive as Delta had a reproductive rate of 6+. Omicron is likely close to chicken pox or measles at this point. "The researchers found that Omicron SARS-CoV-2 infects and multiplies 70 times faster than the Delta variant and original SARS-CoV-2 in human bronchus, which may explain why Omicron may transmit faster between humans than previous variants. Their study also showed that the Omicron infection in the lung is significantly lower than the original SARS-CoV-2, which may be an indicator of lower disease severity. " (Chi Wai 2021)

Omicron enters the cells faster and also replicates much faster than Delta because of the new and improved mutations in the spike protein. The "in lab" studies show that the virus is attacking the bronchi, large lung tubes, and not the terminal lung tissue which is a good sign if it bears out to be the same in infected patients. The anecdotal data appears to support the "in lab" data.

2) It appears that vaccine evasion and general lasting immunity against COVID variant Omicron is not good based on most early reports. However, this is not to say that we are at increased risk of hospitalization or death unless one is already close to this spot by a personal history of significant metabolic disease. Our T and B cells have been educated to many variant changes. As the T and B cells are migrating to the Lymph nodes for training they will pass through many layers of education to protein changes in the spike protein giving us lasting circulating cells with the machinery to crank out lots of antibodies as soon as these changes arrive as with Omicron. The initial response may be suboptimal for preventing disease at all, but the final response is likely to be robust and effective.

3) A really interesting perspective on viral mutations randomness in the NYTimes by Dr. Andrew Pekosz is worth your time. He says in his opinion piece: "As someone who studies viruses, I often hear the phrase, “A dead host is not a good host,” or some version of that. This is probably true for most viruses, and certainly if a virus killed every person it infected it would eventually run out of hosts, which is not a good thing for the virus.
But what is really important is how efficiently the virus spreads. Does making a person very ill provide the virus with some advantage that makes transmission more effective? If the answer to that question is yes, then the virus may continue to make people severely ill because that strategy works. But there’s no high-level “thinking” involved. All viruses mutate, and those mutations occur randomly. A good portion of those mutations don’t affect the virus’s ability to replicate or spread at all. It is these mutations that give the variant a unique fingerprint that can be used to trace chains of transmission and understand how it is spreading locally and globally. Mutations that limit the virus’s ability to replicate are rarely detected because those variants can’t compete with the original virus and quickly go extinct.""Every once in a while, the virus will acquire a mutation that gives it an advantage. Those mutations can affect many different things, but in the end, if this mutated virus can transmit better than the starting virus, there is a good chance that it will go on to become the dominant variant. This is essentially Darwinian evolution by natural selection, performed over weeks or months instead of thousands of years. Will Covid-19 become milder over time? The answer to that question is most likely yes, but it may not have anything to do with the virus evolving to induce milder disease.
Scientists now know that SARS-CoV-2 can, at least to some degree, reinfect people who were previously infected or vaccinated. The combination of prior infections and vaccinations are building immunity in the population. This immunity isn’t perfect because it can’t block infection completely, but it does dampen the disease the virus can induce by shortening the time of infection, reducing the amount of virus that is produced and therefore reducing the symptoms and disease." (Pekosz A. 2021)

This piece is an opinion but has solid historical precedence for the reasoning, As I have stated many times in the past 2 years SARS2 fitness remains a push to higher infectiousness above all. The number of naive hosts that are infected the more mutational events will occur. Thus, it remains a logistical problem for the G8 countries to now prioritize vaccination of the parts of the world with low vaccination rates. We should not be so focused on boosters for healthy low risk Americans and Europeans over unvaccinated global enclaves.

4) Hospitalization and not cases should drive all public policy now. In a well done essay in the NYTimes, Monika Gandhi and Leslie Bienen take this topic to task. "This becomes especially important as case counts become more complicated. A case of Covid-19 doesn’t mean what it used to if you are vaccinated. Most breakthrough infections, which will grow as the number of vaccinated people increases, so far remain mild. Although antibodies wane over time and their effectiveness may be affected by variants, T cells and B cells generated from vaccines should continue to offer protection against severe illness. Right now, in areas of high vaccination, an increase in cases does not necessarily signal a comparable increase in hospitalizations or deaths." (Gandhi et. al. 2021) This is also true for previously infected with natural disease as South Africa and England are demonstrating.

"Singapore, one of the most vaccinated countries in the world, started focusing its daily Covid reports on hospitalizations rather than cases in September. Its Health Ministry reported recently that, over the previous 28 days, of the 41,632 people infected, 98.7 percent had mild or no symptoms." (Gandhi et. al. 2021) Therefore, in a highly vaccinated cohort, 1.3 percent have more than mild symptoms most of which will not die. Again, we see a decoupling of severity with vaccination.

The major issue here is that there are primary schools, universities and businesses that are putting in old school mitigation measures where new policies are needed. A fully vaccinated healthy young person that is masked in school is an exceedingly low spread risk even if positive unless they have significant symptoms. The school should prioritize education at this point unless we see new data that omicron is spreading even with mild disease, fully vaccinated and masked in a young and healthy cohort. Times are different now. We need a different approach.

We are seeing schools, like Cornell, shutting down campuses based on COVID cases despite completely mild disease and no hospitalizations or death following along. (Franklin J. 2021) To what end is this policy? In the pandemic's beginning, preventing hospitalization and death remained the markers of policy variance. Now the goal posts have moved. The argument to close lacks muster now in a vaccinated lower risk world, yet it continues to occur. Strange times indeed.

The individual states' differential COVID policy decisions are amazing incubators of pandemic responses as are these universities choices. Who is thinking about the students well being? If campus closes, by definition, these students have to head home. Is that not sending all of the cases around the country? When does the risk reality finally enter the calculus? Is Cornell going to reimburse the students for time missed and the inability to access resources that have been paid for?

5) From the New England Journal of Medicine: "Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity" (Witberg et. al. 2021) Another study from Europe had similar evidence. (Foltran et. al. 2021)

6) From another study we see more data that at least against delta, spreading out the 2 doses of the mRNA vaccine provided vastly better immunity over time. (Grunau et. al. 2021) This is likely useless data now as we are going to have to eventually switch to an omicron based vaccine in 2022 to slow down the rapid spread of the new evasive mutant. Now comes the question. Do you eventually get one dose of an omicron based vaccine or two and then how far apart. Oh boy, the problems that this variant has developed overnight.

7) Bereaved children - this is a tragic reality that we have seen play out real time in our office. From the New York Times coronavirus update we see that an estimated 167,000 children have lost parents or caregivers to Covid-19. For every four Covid deaths in the U.S., it is estimated that one child is left without a caregiver, a loss that has more severely affected minority communities and frontline workers who were unvaccinated before vaccines were available. If that caregiver was the primary source of family income or even half of it, the family will be in a precarious position moving forward financially. This is not to even mention the social and emotional toll of the death of a parent. This is tragic for a child on all levels.

8) Dr. Wu writes a nice article on the importance of cytotoxic killer T cells in the fight against omicron and any future variants. These cells have a natural capability to kill any cell that has viral particles attached to it. These cells and our other T cells and B cells will give us the ability to handle most variants to the level that moderate to severe disease is rare after vaccination and or natural infection in the past. You may contract omicron as it has evaded the antibodies that you made to date, but it will likely be a mild and shorter illness based on your T and B cell activity. (Wu K. 2021)

Another study in preprint has excellent data that the cytotoxic T cells from Delta are well conserved against omicron. They state: "This analysis examined if the previously identified viral epitopes targeted by CD8+ T-cells in these individuals (n=52 distinct epitopes) are mutated in the newly described Omicron VOC (n=50 mutations). Within this population, only one low-prevalence epitope from the Spike protein restricted to two HLA alleles and found in 2/30 (7%) individuals contained a single amino acid change associated with the Omicron VOC. These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC, and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time." (Redd et. al. 2021)

This is likely the most important study in this newsletter. This is likely the main reason behind milder disease in individuals that get reinfected with COVID omicron and have symptoms. Remember that when we review all of this data regarding waning antibodies and reinfected individuals, we have to look at the totality of the immune response to have a full picture of risk and safety.

9) The Pfizer vaccine for the 2-5 yo age group is on hold till some time in mid to late 2022. This age group has very little risk making this change not terribly traumatic.


Happy Holidays,

Dr. M

Chi Wai HKU News
Garcia Beltran MedRxIV
Nature Article on Omicron
Erman Reuters
Witberg NEJM
Pekosz NYTimes
Gandhi NYTimes
Foltran European Heart J
Grunau JAMANetwork
Franklin NPR
Wu Atlantic
Redd BioRxIV
Doucleff NPR
CDC Variants Page